|By PR Newswire||
|December 10, 2012 12:15 PM EST||
CINCINNATI, Dec. 10, 2012 /PRNewswire-USNewswire/ -- Researchers conducting a preclinical study in mice successfully used targeted molecular therapy to block mostly untreatable nerve tumors that develop in people with the genetic disorder Neurofibromatosis 1 (NF1).
Scientists from Cincinnati Children's Hospital Medical Center report their findings online Dec. 10 in the Journal of Clinical Investigation.
"We can for the first time shrink the large majority of neurofibromas, at least in mice, by using a molecularly targeted treatment," said Nancy Ratner, PhD, principal investigator and program leader for the Cancer Biology and Neural Tumors Program in the Cancer and Blood Disorders Institute at Cincinnati Children's. "At present there is no treatment for these tumors and our data provide strong rationale for testing this therapy in clinical trials for NF1."
Neurofibromas are benign tumors that grow along peripheral nerves in the body. They affect up to half of the people who have NF1. In the United States alone there are 10,000 people with NF1. Fueled initially by mutation of the tumor-suppressing gene NF1, the tumors can grow to become quite large and compress vital organs. They can also transform into deadly malignant peripheral nerve sheath tumors (MPNSTs), the leading cause of death in people with NF1.
The researchers tested an existing experimental drug from Pfizer called PD0325901, which in the current study shrank NF1 tumors in over 80 percent of the mice treated. Study authors report it was "the most dramatic result described to date for neurofibroma bearing mice."
The drug inhibits a protein called MEK, part of a molecular signaling chain that relays genetic instructions to the cell nucleus to promote cell growth. Researchers decided to test the drug after conducting a cross-species bioinformatics computer analysis of mouse and human NF1 tumors. The analysis identified genes and molecules that regulate cell signals driving the growth of neurofibromas and MPNSTs in both species.
The drug is currently being tested in human clinical trials for cancers that involve molecular components similar to those in NF1, in particular the MEK protein.
MEK is a downstream molecular target for a group of cell signaling proteins called Ras-GTPase. The proteins work together in a molecular relay to activate normal cell growth. In the instance of genetic mutation, Ras-GTPase can get stuck in the "on" position and promote hyperactive cell growth, tumor formation or cancer. Overactive Ras-GTPase signaling has been linked to a number of cancers.
In the case of mouse and human NF1 tumors, bioinformatics computer analysis suggested that deregulated Ras-GTPase signaling prompted MEK to stimulate the sustained activity of an enzyme called ERK. To confirm whether this molecular pathway is critical to NF1 tumor growth, researchers tested the MEK-blocking drug in genetically engineered mice.
The mice lacked expression of the NF1 gene and its tumor suppressing protein, causing the animals to develop benign neurofibromas. Scientists also transplanted human malignant peripheral nerve sheath tumor cells into a separate group of genetically receptive mice, which developed their own cancerous tumors.
Researchers then tested different doses of the drug to identify an optimal dose – one that would achieve the maximum amount of tumor shrinking efficiency with the least amount of toxicity. Treatment with PD0325901 reduced the abnormal growth of cells in both benign neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs). It also reduced the volume of tumor feeding blood vessels.
Treated mice with benign neurofibromas had significant shrinkage of their tumors after 60 days, compared to untreated mice. In mice implanted with human MPNSTs, the drug diminished cancerous tumor growth and doubled survival time to 52 days, as compared to untreated animals.
Researchers said overall shrinkage of MPNSTs was modest compared to that achieved in benign tumors, possibly because additional molecular pathways are involved in their formation. They said this suggests that MPNSTs may require a combinatory treatment that includes PD0325901 in conjunction with other therapies.
Mutations of the NF1 gene are frequently found in other cancers, such as glioblastoma, lung adenocarcinoma and ovarian cancer. The researchers said this could open the possibility of studying the Ras-MEK-ERK pathway as molecular target for treating these diseases.
Funding for the study came from: the DAMD Program on Neurofibromatosis for the NF1 Microarray Consortium (DODW81XWH-09-1-0135 and W81XWH-04-1-0273); the Children's Tumor Foundation for support to the NF1 Preclinical Consortium; a National Institutes of Health Bench to Bedside Award for MRI Analyses (NIH-P50-NS05753) and an American Recovery and Reinvestment Act supplement to NIH grant R01-NS28840. The drug was provided by the manufacturer, Pfizer Inc.
About Cincinnati Children's
Cincinnati Children's Hospital Medical Center ranks third in the nation among all Honor Roll hospitals in U.S. News and World Report's 2012 Best Children's Hospitals ranking. It is ranked #1 for neonatology and in the top 10 for all pediatric specialties. Cincinnati Children's is one of the top two recipients of pediatric research grants from the National Institutes of Health and a research affiliate of the University of Cincinnati College of Medicine. It is internationally recognized for improving child health and transforming delivery of care through fully integrated, globally recognized research, education and innovation. Additional information can be found at www.cincinnatichildrens.org.
SOURCE Cincinnati Children's Hospital Medical Center
SYS-CON Events announced today that ContentMX, the marketing technology and services company with a singular mission to increase engagement and drive more conversations for enterprise, channel and SMB technology marketers, has been named “Sponsor & Exhibitor Lounge Sponsor” of SYS-CON's 18th Cloud Expo, which will take place on June 7-9, 2016, at the Javits Center in New York City, New York. “CloudExpo is a great opportunity to start a conversation with new prospects, but what happens after the...
May. 31, 2016 01:30 AM EDT Reads: 1,446
In the rush to compete in the digital age, a successful digital transformation is essential, but many organizations are setting themselves up for failure. There’s a common misconception that the process is just about technology, but it’s not. It’s about your business. It shouldn’t be treated as an isolated IT project; it should be driven by business needs with the committed involvement of a range of stakeholders.
May. 31, 2016 12:15 AM EDT Reads: 2,755
The IoTs will challenge the status quo of how IT and development organizations operate. Or will it? Certainly the fog layer of IoT requires special insights about data ontology, security and transactional integrity. But the developmental challenges are the same: People, Process and Platform. In his session at @ThingsExpo, Craig Sproule, CEO of Metavine, will demonstrate how to move beyond today's coding paradigm and share the must-have mindsets for removing complexity from the development proc...
May. 30, 2016 10:00 PM EDT Reads: 2,029
SYS-CON Events announced today that EastBanc Technologies will exhibit at SYS-CON's 18th International Cloud Expo®, which will take place on June 7-9, 2016, at the Javits Center in New York City, NY. EastBanc Technologies has been working at the frontier of technology since 1999. Today, the firm provides full-lifecycle software development delivering flexible technology solutions that seamlessly integrate with existing systems – whether on premise or cloud. EastBanc Technologies partners with p...
May. 30, 2016 09:00 PM EDT Reads: 2,459
SYS-CON Events announced today that AppNeta, the leader in performance insight for business-critical web applications, will exhibit and present at SYS-CON's @DevOpsSummit at Cloud Expo New York, which will take place on June 7-9, 2016, at the Javits Center in New York City, NY. AppNeta is the only application performance monitoring (APM) company to provide solutions for all applications – applications you develop internally, business-critical SaaS applications you use and the networks that deli...
May. 30, 2016 06:00 PM EDT Reads: 2,674
As organizations shift towards IT-as-a-service models, the need for managing and protecting data residing across physical, virtual, and now cloud environments grows with it. Commvault can ensure protection, access and E-Discovery of your data – whether in a private cloud, a Service Provider delivered public cloud, or a hybrid cloud environment – across the heterogeneous enterprise. In his general session at 18th Cloud Expo, Randy De Meno, Chief Technologist - Windows Products and Microsoft Part...
May. 30, 2016 05:30 PM EDT Reads: 805
The cloud era has reached the stage where it is no longer a question of whether a company should migrate, but when. Enterprises have embraced the outsourcing of where their various applications are stored and who manages them, saving significant investment along the way. Plus, the cloud has become a defining competitive edge. Companies that fail to successfully adapt risk failure. The media, of course, continues to extol the virtues of the cloud, including how easy it is to get there. Migrating...
May. 30, 2016 05:30 PM EDT Reads: 778
WebRTC is bringing significant change to the communications landscape that will bridge the worlds of web and telephony, making the Internet the new standard for communications. Cloud9 took the road less traveled and used WebRTC to create a downloadable enterprise-grade communications platform that is changing the communication dynamic in the financial sector. In his session at @ThingsExpo, Leo Papadopoulos, CTO of Cloud9, will discuss the importance of WebRTC and how it enables companies to fo...
May. 30, 2016 04:30 PM EDT Reads: 2,642
As machines are increasingly connected to the internet, it’s becoming easier to discover the numerous ways Industrial IoT (IIoT) is helping to shape the business world. This is exactly why we have decided to take a closer look at this pervasive movement and to examine the desire to connect more things! Now if you need a refresher on IIoT and how it is changing the world, take a moment and listen to Greg Gorbach with ARC Advisory Group. Gorbach believes, "IIoT will significantly change the worl...
May. 30, 2016 04:30 PM EDT Reads: 2,113
SYS-CON Events announced today the Docker Meets Kubernetes – Intro into the Kubernetes World, being held June 9, 2016, in conjunction with 18th Cloud Expo | @ThingsExpo, at the Javits Center in New York, NY. Register for 'Docker Meets Kubernetes Workshop' Here! This workshop led by Sebastian Scheele, co-founder of Loodse, introduces participants to Kubernetes (container orchestration). Through a combination of instructor-led presentations, demonstrations, and hands-on labs, participants learn ...
May. 30, 2016 03:00 PM EDT Reads: 2,093
The IoT is changing the way enterprises conduct business. In his session at @ThingsExpo, Eric Hoffman, Vice President at EastBanc Technologies, discuss how businesses can gain an edge over competitors by empowering consumers to take control through IoT. We'll cite examples such as a Washington, D.C.-based sports club that leveraged IoT and the cloud to develop a comprehensive booking system. He'll also highlight how IoT can revitalize and restore outdated business models, making them profitable...
May. 30, 2016 02:00 PM EDT Reads: 3,097
SYS-CON Events announced today that MangoApps will exhibit at SYS-CON's 18th International Cloud Expo®, which will take place on June 7-9, 2016, at the Javits Center in New York City, NY. MangoApps provides modern company intranets and team collaboration software, allowing workers to stay connected and productive from anywhere in the world and from any device. For more information, please visit https://www.mangoapps.com/.
May. 30, 2016 01:30 PM EDT Reads: 1,162
In his session at 18th Cloud Expo, Andrew Cole, Director of Solutions Engineering at Peak 10, will discuss how the newest technology advances are reducing the cost and complexity of traditional business continuity and disaster recovery solutions. Attendees will: Learn why having a full disaster recovery strategy is more important now than ever before Explore the key drivers of a successful disaster recovery solution Achieve measurable operational and business value from a disaster recovery ...
May. 30, 2016 12:00 PM EDT Reads: 1,515
SYS-CON Events announced today the How to Create Angular 2 Clients for the Cloud Workshop, being held June 7, 2016, in conjunction with 18th Cloud Expo | @ThingsExpo, at the Javits Center in New York, NY. Angular 2 is a complete re-write of the popular framework AngularJS. Programming in Angular 2 is greatly simplified. Now it’s a component-based well-performing framework. The immersive one-day workshop led by Yakov Fain, a Java Champion and a co-founder of the IT consultancy Farata Systems and...
May. 30, 2016 12:00 PM EDT Reads: 4,130
SYS-CON Events announced today that Super Micro Computer, Inc., a global leader in Embedded and IoT solutions, will exhibit at SYS-CON's 18th International Cloud Expo®, which will take place on June 7-9, 2016, at the Javits Center in New York City, NY. Supermicro (NASDAQ: SMCI), the leading innovator in high-performance, high-efficiency server technology, is a premier provider of advanced server Building Block Solutions® for Data Center, Cloud Computing, Enterprise IT, Hadoop/Big Data, HPC and ...
May. 30, 2016 12:00 PM EDT Reads: 820